Virtual Screening and Validation of Affinity DNA Functional Ligands for IgG Fc Segment

• Published in: International journal of molecular sciences Vol. 25; no. 16; p. 8681
• Main Authors: Yang, Qianyu, Liu, Zhiwei, Xu, Xinrui, Wang, Jiang, Du, Bin, Zhang, Pengjie, Liu, Bing, Mu, Xihui, Tong, Zhaoyang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.08.2024; MDPI
• Subjects: affinity; Antibodies; Antigens; Binding Sites; Biosensing Techniques - methods; Biosensors; Cost analysis; DNA - chemistry; DNA - metabolism; DNA functional ligand; Fc segment; Fourier transforms; Humans; Immunoglobulin Fc Fragments - chemistry; Immunoglobulin Fc Fragments - metabolism; Immunoglobulin G - chemistry; Immunoglobulin G - metabolism; Interfaces; Ligands; Methods; molecular docking; Molecular Docking Simulation; Molecular weight; Protein Binding; RNA-protein interactions; Sensors; virtual screening; DNA functional ligand; molecular docking; virtual screening; Fc segment; affinity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25168681

The effective attachment of antibodies to the immune sensing interface is a crucial factor that determines the detection performance of immunosensors. Therefore, this study aims to investigate a novel antibody immobilization material with low molecular weight, high stability, and excellent directional immobilization effect. In this study, we employed molecular docking technology based on the ZDOCK algorithm to virtually screen DNA functional ligands (DNAFL) for the Fc segment of antibodies. Through a comprehensive analysis of the key binding sites and contact propensities at the interface between DNAFL and IgG antibody, we have gained valuable insights into the affinity relationship, as well as the principles governing amino acid and nucleotide interactions at this interface. Furthermore, molecular affinity experiments and competitive binding experiments were conducted to validate both the binding ability of DNAFL to IgG antibody and its actual binding site. Through affinity experiments using multi-base sequences, we identified bases that significantly influence antibody-DNAFL binding and successfully obtained DNAFL with an enhanced affinity towards the IgG Fc segment. These findings provide a theoretical foundation for the targeted design of higher-affinity DNAFLs while also presenting a new technical approach for immunosensor preparation with potential applications in biodetection.